title: Differential clot stabilising effects of rFVIIa and rFXIII-A2 in  whole blood from thrombocytopenic patients and  healthy volunteers.
abstract: The haemostatic effect of recombinant activated factor VII (rFVIIa;NovoSeven) in thrombocytopenic patients has been a matter of controversy. Haemostasis by rFVIIa occurs via FVIIa-mediated thrombin generation in a platelet-dependent manner and may therefore be suboptimal in patients without functional platelets. Under such conditions, a clot-stabilizing agent, such as factor XIII (FXIII), may supplement the effect ofrFVIIa and improve haemostasis. Recombinant factor XIII (rFXIII-A2) is produced as an A2 homodimer of the FXIII A subunit and is equivalent to cellular FXIII normally found in platelets. The combined effects of rFVIIa andrFXIII-A2 were evaluated in clot lysis assays using factor XIII-deficient plasma and by whole blood thrombelastography (TEG) analysis from normal donors and thrombocytopenic stem cell transplantation patients. Clotting time was shortened by rFVIIa (0.6-10 microg/ml). rFVIIa only modestly improved anti-fibrinolysis,whereas rFXIII-A2 (0-20 microg/ml) enhanced anti-fibrinolysis without effect on clotting time. TEG analysis showed rFVIIa shortened the clotting time, and enhanced clot development, maximal mechanical strength and resistance to fibrinolysis, whereas, rFXIII-A2 enhanced clot development,maximal mechanical strength and markedly enhanced resistance to fibrinolysis. These data illustrate that rFVIIa and rFXIII-A2 contribute to clot formation and stability by different mechanisms suggesting enhanced haemostatic efficacy by combining these agents.
authors.affiliation: Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. per.johansson@rh.hosp.dk
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.forename: Niels
authors.initials: N
authors.lastname: Jacobsen
authors.forename: Dorthe
authors.initials: D
authors.lastname: Viuff
authors.forename: Eva H N
authors.initials: EH
authors.lastname: Olsen
authors.forename: Rasmus
authors.initials: R
authors.lastname: Rojkjaer
authors.forename: Søren
authors.initials: S
authors.lastname: Andersen
authors.forename: Lars C
authors.initials: LC
authors.lastname: Petersen
authors.forename: Marianne
authors.initials: M
authors.lastname: Kjalke
mesh_terms: D001772:Blood Cell Count; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015942:Factor VIIa / Q000494:pharmacology*; D026122:Factor XIIIa / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D011994:Recombinant Proteins / Q000494:pharmacology; D033581:Stem Cell Transplantation; D013916:Thrombelastography / Q000379:methods; D013921:Thrombocytopenia / Q000097:blood* / Q000628:therapy
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D026122:Factor XIIIa; D015942:Factor VIIa